The former Spain, Sevilla and Real Madrid boss joined Wolves in November with the club in the relegation zone and successfully guided the club to safety by the end of the Premier League season.
It had been suggested Lopetegui had been unhappy with the club's lack of progress in the transfer market and had wanted his contract terminated with immediate effect.
A Wolves statement read: "Lopetegui joined Wolves in November and successfully guided the club to Premier League safety, however, the head coach and club acknowledged and accepted their differences of opinion on certain issues and agreed that an amicable end to his contract was the best solution for all parties.
"Talks have been ongoing in recent weeks, held with the utmost respect and cordiality, affording the club time and space to begin work on finding a successor, while also ensuring that Julen and his backroom staff could continue their planned preparation to ensure the playing squad would be in the best possible condition for the start of the Premier League season.
"Lopetegui arrived with the club bottom of the Premier League, and won nine league games from that point, including against Liverpool and Tottenham Hotspur at Molineux, which helped the Old Gold secure a sixth successive top-flight campaign.
"As well as Lopetegui, his backroom team, consisting of Pablo Sanz, Juan Peinado, Oscar Caro, Edu Rubio, Borja De Alba Alonso and Daniel Lopetegui, will all depart the club too."
Speaking as part of the same statement, Lopetegui said: "I wish Wolves and everybody at the club the very best of luck for the future, and thank them for the opportunity granted at the time to take charge of this wonderful club.
"Also, of course, I want to thank the players, who have always given the maximum to achieve our objectives, and especially the fans that made me feel like one of them from the very first moment and have always been amazing to me, my staff and my family.”
Sporting director Matt Hobbs said: "On behalf of everyone at the club I’d like to thank Julen and his staff for their dedication and hard work during their time at the football club.
"They were brought in with the primary aim of keeping the club in the Premier League last season, an objective which they achieved with games to spare."
Former Bournemouth boss Gary O'Neil is reportedly being lined up to take the reigns at Molineux, with Wolves set to begin their Premier League campaign away to Manchester United on Monday.
